Mulder Jorn, van Stuijvenberg Odile C, van Hennik Paula B, Voest Emile E, Pasmooij Anna M G, Stoyanova-Beninska Violeta, de Boer Anthonius
Dutch Medicines Evaluation Board, Utrecht, Netherlands.
The Netherlands Cancer Institute, Amsterdam, Netherlands.
Front Med (Lausanne). 2022 Jun 14;9:893400. doi: 10.3389/fmed.2022.893400. eCollection 2022.
There are currently four anti-cancer medicinal products approved for a tissue-agnostic indication. This is an indication based on a common biological characteristic rather than the tissue of origin. To date, the regulatory experience with tissue-agnostic approvals is limited. Therefore, we compared decision-making aspects of the first tissue-agnostic approvals between the Food and Drug Administration (FDA), European Medicines Agency (EMA) and Pharmaceuticals and Medical Devices Agency (PMDA). Post-marketing measures (PMMs) related to the tissue-agnostic indication were of specific interest. The main data source was the publicly available review documents. The following data were collected: submission date, approval date, clinical trials and datasets, and PMMs. At the time of data collection, the FDA and PMDA approved pembrolizumab, larotrectinib, and entrectinib for a tissue-agnostic indication, while the EMA approved larotrectinib and entrectinib for a tissue-agnostic indication. There were differences in analysis sets (integrated vs. non-integrated), submission dates and requests for data updates between agencies. All agencies had outstanding issues that needed to be addressed in the post-market setting. For pembrolizumab, larotrectinib and entrectinib, the number of imposed PMMs varied between one and eight, with the FDA requesting the most PMMs compared to the other two agencies. All agencies requested at least one PMM per approval to address the remaining uncertainties related to the tissue-agnostic indication. The FDA and EMA requested data from ongoing and proposed trials, while the PMDA requested data from use-result surveys. Confirmation of benefit in the post-marketing setting is an important aspect of tissue-agnostic approvals, regardless of agency. Nonetheless, each approach to confirm benefit has its inherent limitations. Post-marketing data will be essential for the regulatory and clinical decisions-making of medicinal products with a tissue-agnostic indication.
目前有四种抗癌药物被批准用于组织非特异性适应症。这是一种基于共同生物学特征而非起源组织的适应症。迄今为止，组织非特异性批准的监管经验有限。因此，我们比较了美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）和日本药品和医疗器械管理局（PMDA）首次组织非特异性批准的决策方面。与组织非特异性适应症相关的上市后措施（PMMs）是特别关注的对象。主要数据来源是公开的审评文件。收集了以下数据：提交日期、批准日期、临床试验和数据集以及PMMs。在数据收集时，FDA和PMDA批准了帕博利珠单抗、拉罗替尼和恩曲替尼用于组织非特异性适应症，而EMA批准了拉罗替尼和恩曲替尼用于组织非特异性适应症。各机构在分析集（整合型与非整合型）、提交日期和数据更新要求方面存在差异。所有机构都有需要在上市后环境中解决的未决问题。对于帕博利珠单抗、拉罗替尼和恩曲替尼，实施的PMMs数量在1至8项之间，与其他两个机构相比，FDA要求的PMMs最多。所有机构每项批准至少要求一项PMM，以解决与组织非特异性适应症相关的剩余不确定性。FDA和EMA要求提供正在进行和拟进行试验的数据，而PMDA要求提供使用结果调查的数据。无论哪个机构，在上市后环境中确认获益都是组织非特异性批准的一个重要方面。尽管如此，每种确认获益的方法都有其固有的局限性。上市后数据对于具有组织非特异性适应症的药品的监管和临床决策至关重要。
